Research Overview

Multistage Cancer Development in the Mouse Epidermis

Multistage Cancer Development in the Mouse Epidermis

My laboratory is focused on understanding signaling pathways that regulate normal homeostasis and cancer progression in squamous epithelia. A major cause of skin cancer and squamous cell cancers in the oral cavity and esophagus is environmental and lifestyle exposure to physical and chemical carcinogens. Non-melanoma skin cancer including both basal cell carcinoma and squamous cell carcinoma is the most frequent cancer among Caucasian populations, with incidence rates matching all other cancers combined in these groups. Although exposure to ultraviolet radiation from the sun is the major risk factor for cutaneous SCC, other risk factors also include chronic inflammation, and wounding, as well as exposure to arsenic, tobacco and coal tar products. The multistage mouse skin carcinogenesis model has been instrumental in defining the basic biology of squamous cell carcinoma (SCC) development in the skin and other epithelia.

Main Research Areas

  • The role of Transforming Growth Factor Beta (TGFβ) and its signaling pathway in the regulation of skin tumor promotion and progression, primarily examining this cytokines effects on cutaneous inflammation and tumor development in vivo and on Ras oncogene-induced senescence in vitro

  • Regulation of the unfolded protein response (UPR) by oncogenic pathways. The role of the UPR in cellular responses to oncogene activation and its importance in skin and lung tumor development. Utilization of the UPR as a target for prevention or treatment of cancer.

  • Role of distinct tumor intitiating cell populations in the generation of specific proinflammatory or immunosuppressive tumor immune microenvironments. Role of B cells in driving specific tumor immune microenvironments.